Efficacy of immune checkpoint inhibitors in non-small cell lung cancer: A systematic review and meta-analysis.

Background: Immune checkpoint inhibitors (ICIs) have demonstrated remarkable efficacy in non-small cell lung cancer (NSCLC). However, only a minority of NSCLC patients benefit from ICIs, and whether the magnitude of benefit is specific factor-dependent remains unclear. We performed a systematic review to improve our understanding of clinicopathologic and biomolecular features associated with improved survival upon treatment with ICIs for NSCLC. Methods: We searched PubMed, Web of Science, Embase, and Scopus from database inception to August 31, 2021, for randomized controlled trials (RCTs) comparing overall survival (OS) in NSCLC treated with ICIs vs control therapies. We calculated the pooled OS hazard ratio (HR) and 95% CI in subgroups using a random-effects model, and assessed the heterogeneity between the paired estimates using an interaction test. Results: A total of 23 RCTs involving 15,829 patients were included. We found that wild-type EGFR, high PD-L1 expression, and high bTMB were associated with a significant OS benefit from ICIs, but not mutant EGFR, low PD-L1 expression, and low bTMB. The differences of OS benefit between wild-type and mutant EGFR (HR=1.53, 95%CI 1.13-2.08), high and low PD-L1 (HR=1.35; 95%CI 1.14-1.61), high and low bTMB (HR=1.71; 95%CI 1.17-2.52) were statistically significant. OS benefit was found in all subgroups regardless of sex, age, ECOG PS, histology, smoking history, baseline brain metastasis, race, and region, and the interaction test demonstrated no significant difference of the OS benefit between these opposed subgroups (e.g. male vs female). Conclusions: Wild-type EGFR, high PD-L1 expression, and high bTMB are associated with a greater magnitude of efficacy from ICIs vs control therapies in NSCLC. However, the administration of ICIs should not be restricted to other clinicopathological factors (sex, smoking history, race, etc.).